Water → (RS)-1-[2-(4-Acetyl-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluorophenyl)-2-methylthiazol-4-yl]methanone

HRID 598594Notes

Reaction equation

HRID 598594 reaction equation
Br[C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][N:13]3[C:18]([C:20]3[N:21]=[C:22]([CH3:32])[S:23][C:24]=3[C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[O:19])[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:38]([O:40]CC)=[CH2:39])CCC.O>O1CCOCC1.Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:38]([C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][N:13]3[C:18]([C:20]3[N:21]=[C:22]([CH3:32])[S:23][C:24]=3[C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[O:19])[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)(=[O:40])[CH3:39]

Participants

7

Reactant 3

HCID 962Water2×HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 17973675HCID 17973675, compound

Product 1

HCID 17973678(RS)-1-[2-(4-Acetyl-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluorophenyl)-2-methylthiazol-4-yl]methanone

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 178418397HCID 178418397, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

To a deoxygenated solution of (RS)-1-[2-(4-bromo-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluorophenyl)-2-methylthiazol-4-yl]methanone, E66 (200 mg, 0.39 mmol) in anhydrous 1,4-dioxane (10 ml) was added tributyl(1-ethoxyvinyl)tin (155 mg, 0.43 mmol) and tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.026 mmol). The resultant mixture was refluxed under argon for 20 h. Further tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.052 mmol) was added and refluxing continued for a further 24 h. On cooling, water (15 ml) and 5N hydrochloric acid (10 drops) were added and the mixture stirred at room temperature for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organics were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (silica gel,

Workup

  1. temperaturerefluxing
  2. temperatureOn cooling
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-a84e43b81ead4610a7844f55980ec647
Source dataset
uspto-grants-2011_03
Patent number
US07897618B2

Reaction notes

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